This research program aims at elucidating the biochemical basis of the psychopharmacological effects produced by some of the serotonin depletors in cerebral function, namely, p-chlorophenylalanine (p-CP) and p-chloroamphetamine (p-CA). These compounds are important psychopharmacological agents influencing such functions as sleep, pain, sexuality, gross and consumatory behavior in rats and human beings. The appearance of changes in the above events is largely related to their effects on serotonin metabolism. p-Chloroamphetamine, through its being neurotoxic to the serotonergic system, and p-CP, by being a specific, selective, irreversible inactivator of 5-hydroxytryptophan synthesis, exert their powerful psychopharmacological effects. In view of our recent investigations, it is our thesis that inactivation of tryptophan and phenylalanine hydroxylases results from the substitution of amino acid(s) at or near the active center. Evidence for substitution in these enzymes via protein synthesis was obtained; however, the inactivation of these hydroxylases was suppressed in animals pretreated with inhibitors of protein synthesis prior to administration of p-CP in vivo. BIBLIOGRAPHIC REFERENCES: Sherman, A.D. and Gal, E. M., H3-p-Chloroamphetamine: Cerebral Levels and Distribution, Psychopharmacol. Comm. 1, 261-273, 1975. Gal, E.M., Function and Control of Cerebral Tryptophan-5-Hydroxylase, in Structure and Function of Synapses, K. Kuriyama, ed., Ishiyaku Shuppan Publishing Company, Tokyo, (in press, l976).